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Series GSE41336 Query DataSets for GSE41336
Status Public on Jan 18, 2013
Title Cultured Cyto and Syncytio-trophoblast samples exposed to varying degrees of hypoxia (methylation)
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast.
Overall design DNA from 2 cell types from 5 placentas exposed to 3 different conditions of hypoxia (1%,8%,20%) and treated with 3 levels of vitamin D were bisulfite converted and run on the Illumina HumanMethylation450 BeadChip
Contributor(s) Yuen RC, Chen B, Blair JD, Robinson WP, Nelson DM
Citation(s) 23314690
Submission date Oct 03, 2012
Last update date Mar 22, 2019
Contact name Wendy Robinson
Organization name University of British Columbia
Department Medical Genetics
Lab Robinosn
Street address 950 W 28th Ave
City Vancouver
State/province BC
ZIP/Postal code V5Z 4H4
Country Canada
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (90)
GSM1015054 Cyto 1% oxygen 0Vitd (methylation) 92
GSM1015055 Cyto 1% oxygen 10Vitd (methylation) 92
GSM1015056 Cyto 1% oxygen 100Vitd (methylation) 92
This SubSeries is part of SuperSeries:
GSE41341 Cultured Cyto and Syncytio-trophoblast samples exposed to varying degrees of hypoxia
BioProject PRJNA176597

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE41336_RAW.tar 183.1 Mb (http)(custom) TAR
GSE41336_normalized.txt.gz 216.6 Mb (ftp)(http) TXT
GSE41336_signal_intensities.txt.gz 213.0 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data are available on Series record

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